Platelet-derived growth factor (PDGF) is a disulfide-linked dimer consisting of two related polypeptide chains, designated PDGF A and PDGF B, that are the products of distinct genes. The gene encoding the human PDGF B chain is the normal counterpart of the v-sis oncogene. Solid phase PDGFR binding assays, PDGF B deletion mutants, and mab sisI were utilized to demonstrate that the beta PDGFR is bound exclusively through the PDGF B chain of the PDGF AB heterodimer, while the alpha PDGFR interacts with either the PDGF A or B chain of the nascent heterodimer. PDGF A and PDGF B have distinct transforming phenotypes and cellular locations. PDGF B contains two subdomains (106-114 and 135-144) which were identified as critical for beta receptor interaction. Eighteen substitution mutants in which PDGF B amino acid residues were substituted into PDGF A demonstrated that five PDGF B residues were essential to convert PDGF A to a PDGF B transforming molecule. further studies will be directed at identification of competitive antagonists among these residues to be used for blocking PDGF-mediated responses. A potently neutralizing monoclonal antibody (mab) to the human alpha PDGFR was raised by immunizing with 32D alphaR transfectants. Mab recognized alpha PDGFRs in several species, as well as alpha PDGFRs in human tumor cell lines. Mab alphaR1 was also useful for inhibiting autocrine growth stimulation of 32D alpha PDGFR transfectants expressing either PDGF AA or PDGF BB.